What life is


Molecular biology of the gene

Biologists in the 20th century have not only discovered the rules of genetics, but also the link between genes and traits. The discovery of the structure of the DNA double helix in 1953 has provided an explanation for both inheritance, the faithful copying of genetic information during reproduction, and the genetic code, the rules of how genetic information is read and used to make proteins, the work horses of cells. Francis Crick, the codiscoverer of the DNA structure, was also instrumental in cracking the code. He proposed the central dogma of molecular biology that says that genetic information flows from DNA via RNA to proteins. Armed with this concept, molecular biologists soon found the codon nature of the genetic code. A codon is a three letter DNA instruction to use one particular amino acid in a protein. A string of codons in a gene (nucleotide sequence) thus results in a string of amino acids in a protein (amino acid sequence). This linear correspondence of the molecule structure of a nucleic acid polymer to make a amino acid polymer is universal. That means the same code is used in all known organisms. In a few cases, the exact assignment of which codon sequence is used for which amino acid differs. Differences are found in organellar DNA (mitochondrion and chloroplasts) and DNA of some microorganisms. The latter reflects on the enormous genetic diversity of microorganisms, which is much broader than diversity among plants and animals.

The central dogma of molecular biology had soon to be modified when it was discovered that some viruses contain RNA instead of DNA in their genome, and that they are able to make a DNA copy after successfully infecting a host cell. They use a protein called reverse transcriptase, an enzyme that revolutionized molecular biology because it allows to make genes from RNA. This particular process is now used to study gene expression patterns in organisms and get an understanding of how organisms use their genes to carry out their metabolic and physiological functions. It also demonstrated the central role of RNA in modern organisms. Together with proteins, they control how and when genes are being used. Today, the central dogma means that genetic information flows from nucleic acid to nucleic acid, and from nucleic acid to protein, but never from protein to nucleic acid. While proteins have control over the copying mechanism of nucleic acids, proteins cannot make copies of themselves or independent of the genetic blueprint.

Other enzymes were also central to advancement of genetic engineering. Restriction enzymes that recognize short, but highly specific sequences allow the cutting of DNA into smaller fragments, which in turn can be spliced together in any combination with the help of ligases. Since the genetic code and structure of DNA is universal, this cut and past technique allows the recombination of DNA from different organisms, as different as bacteria and humans. Recombinant DNA technology has allowed construction of microorganisms, plants, and farm animals with particular novel traits. Such genetically modified organisms provide better growth conditions, longer shelf-life of grocery items, but also the development of novel medicine. Genetic engineering has been particularly useful for drug development and drug production. One of the first medical applications of recombinant DNA technology was the production of the human insulin (a protein) in bacterial cell culture. Here the human gene with the instructions for the amino acid sequence of insulin has been spliced into a bacterial DNA (plasmid). The bacterial cells can be easily grown in large numbers and triggered to synthesize and release the insulin protein for isolation and purification.

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 Copyright © 1999-2011 Lukas K. Buehler